Effects of parasites on the gene expression of nitric oxide synthase and chemokine in macrophages

寄生虫对巨噬细胞一氧化氮合酶和趋化因子基因表达的影响

基本信息

批准号：
06670257
负责人：
FUKUMOTO Soji
金额：
$ 1.41万
依托单位：
TOTTORI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06670257/
关键词：
parasite macrophage nitric oxide synthase chemokine gene expression northern blot Spirometra erimacei 擬充尾虫 TNFα プレロセルコイド一酸化窒素合成酸素 Northern Blotting 遺伝子発現抑制インターフェロン-γ

项目摘要

Nitric oxide (NO) is important in the ability of mouse macrophages to kill infectious organisms including parasites. An inducible form of NO synthase (iNOS) is responsible for high output generation of NO by macrophages after stimulation with cytokines and/or LPS.Chemoattactant peptides termed chemokine are important components of the inflammatory response. Alive plerocercoids of Spirometra erinacei suppressed the mRNA expression of iNOS and JE,murine homologue of monocyte chemotactic protein-1, and nitrite production of macrophages stimulated with IFN-gamma and LPS in vitro. Excretory/secretory (ES) products from plerocercoids also suppressed the induced iNOS and JE mRNA and reduce nitrite production in a dose dependent manner. The suppression of iNOS mRNA levels in macrophages cultured for 24 h with ES products varied with the nature of the stimuli ; IFN gamma/LPS-induced iNOS mRNA levels were effected less than were iNOS mRNA levels induced by IFNgamma/IL-2 or IFNgamma/TNFalpha. Similar findings were obtained when nitrite production was measured. Thus mRNA levels appear to be the primary target of ES products. The expression of the glyceraldehyde-3-phosphate dehydrogenase gene was unaffected by the ES products. The NO donor drugs, S-nitroso-acetyl-penicillamine or diethylamine dinitric oxide, were unable to kill plerocercoids in vitro in the absence of macrophages, therefore NO might not be important in the host's defense mechanism to plerocercoids. It is supposed that a main physiological role of this inhibitory factor in ES products might be selectively down regulation of LPS-inducible gene expressions such as chemokines (JE and gro-alpha/KC) thereby preventing the accumlation of leukocytes, but not preventing the iNOS expression specifically.

一氧化氮（NO）对于小鼠巨噬细胞杀死包括寄生虫在内的传染性生物体的能力非常重要。诱导型 NO 合酶 (iNOS) 负责巨噬细胞在细胞因子和/或 LPS 刺激后大量产生 NO。称为趋化因子的趋化肽是炎症反应的重要组成部分。活的猴头菇可抑制 iNOS 和 JE、单核细胞趋化蛋白 1 的鼠同源物的 mRNA 表达，以及体外用 IFN-γ 和 LPS 刺激的巨噬细胞的亚硝酸盐产生。来自多头尾蠹的排泄/分泌 (ES) 产物还抑制诱导的 iNOS 和 JE mRNA，并以剂量依赖性方式减少亚硝酸盐的产生。用ES产品培养24小时的巨噬细胞中iNOS mRNA水平的抑制随刺激的性质而变化； IFNγ/LPS诱导的iNOS mRNA水平受到的影响小于IFNγ/IL-2或IFNγ/TNFα诱导的iNOS mRNA水平。当测量亚硝酸盐的产生时，也得到了类似的结果。因此 mRNA 水平似乎是 ES 产品的主要目标。 3-磷酸甘油醛脱氢酶基因的表达不受ES产物的影响。 NO供体药物S-亚硝基乙酰青霉胺或二乙胺二氧化氮在没有巨噬细胞的情况下无法在体外杀死多尾蚴，因此NO在宿主对多尾蚴的防御机制中可能并不重要。据推测，ES 产物中该抑制因子的主要生理作用可能是选择性下调 LPS 诱导基因表达，如趋化因子（JE 和 gro-alpha/KC），从而防止白细胞积聚，但不能防止 iNOS具体表达。